A brief review on long noncoding RNAs: a new paradigm in breast cancer pathogenesis, diagnosis and therapy

Abstract

With the development of technologies such as microarrays and RNA deep sequencing, long noncoding RNAs (lncRNAs) have become the focus of cancer investigations. LncRNAs, nonprotein-coding RNA molecules longer than 200 nucleotides, are dysregulated in many human diseases, especially in cancers. Recent studies have demonstrated that lncRNAs play a key regulatory role in gene expression and cancer biology through diverse mechanisms, including chromosome remodeling and transcriptional and post-transcriptional modifications. The expression levels of specific lncRNAs are attributed to prognosis, metastasis, and recurrence of cancer. LncRNAs are often involved in various biological processes, such as regulation of alternative splicing of mRNA, protein activity, and epigenetic modulation or silencing of the microRNAs, via discrete mechanisms. Deregulated levels of lncRNAs are shown in diverse tumors, including breast cancer. Based on latest research data, the tissue-specific expression signature of lncRNAs may represent the potential to discriminate normal and tumor tissue or even the different stages of breast cancer, which makes them clinically beneficial as possible biomarkers in the diagnosis and prognosis or therapeutic targets. In this brief review, we summarize some recent researches in the context of lncRNAs' roles in breast cancer pathogenesis and their potential to serve as diagnostic, predictive, and prognostic biomarkers and novel targets for breast cancer treatment.

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The over-expression of FGFR4 could influence the features of gastric cancer cells and inhibit the efficacy of PD173074 and 5-fluorouracil towards gastric cancer

Abstract

The aim was to investigate the function of fibroblast growth factor receptor 4 (FGFR4) in gastric cancer (GC) and explore the treatment value of agent targeted to FGFR4. Function assays in vitro and in vivo were performed to investigate the discrepancy of biological features among the GC cells with different expression of FGFR4. GC cells were treated with the single and combination of PD173074 (PD, an inhibitor of FGFR4) and 5-fluorouracil (5-Fu). The invasion ability were stronger, and the apoptosis rates were lower in MGC803 and BGC823 cells treated with FGFR4-LV5 (over-expression of FGFR4 protein) (P < 0.05). The proliferation ability of GC cells is reduced when treated by the single and combination of 5-Fu and PD while that of the FGFR4-LV5 group was less inhibited compared with control group (P < 0.05). The apoptosis rates are remarkably increased in GC cells treated with the single and combination of 5-Fu and PD (P < 0.05). However, the apoptosis rate obviously is reduced in GC cells treated with FGFR4-LV5 compared with control group (P < 0.05). The expression of PCNA and Bcl-XL is remarkably decreased, and the expression of Caspase-3 and cleaved Caspase-3 is obviously increased in GC cells treated with the single and combination of 5-Fu and PD. The tumor volumes of nude mice in FGFR4-LV5 group were much more increased (P < 0.05). The over-expression of FGFR4 enhanced the proliferation ability of GC in vitro and in vivo. The combination of 5-Fu and PD exerted synergetic effect in weakening the proliferation ability and promoting apoptosis in GC cells, while the over-expression of FGFR4 might inhibit the efficacy of two drugs.

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Correlation of IL-27 genetic polymorphisms with the risk and survival of cervical cancer in a Chinese Han population

Abstract

Interleukin-27 (IL-27) has been recognized as a pleiotropic cytokine with both pro- and anti-inflammatory properties. However, there are no data about the role of IL-27 polymorphism in the development of cervical cancer. A hospital-based case–control study was conducted in 380 patients with cervical cancer and 380 healthy controls to investigate the possible associations of IL-27 gene polymorphisms (−964A/G, 2905T/G, and 4730T/C), with susceptibility to cervical cancer and clinical outcome. Our results suggested that the IL-27 2905T/G was significantly associated with a decreased risk of cervical cancer (TG vs. TT, odds ratio (OR) = 0.77; 95 % confidence interval (CI) = 0.60–0.86; GG vs. TT, OR = 0.95; 95 % CI = 0.72–0.96; TG+GG vs. TT, OR = 0.87; 95 % CI = 0.65–0.94). However, the genotype and allele frequencies of IL-27 (−964A/G and 4730T/C) polymorphisms in cervical cancer patients were not significantly different from controls. Further analysis showed IL-27 2905T/G genotypes were associated with advanced tumor stages of cervical cancer patients. More interestingly, the IL-27 2905T/G genotypes were statistically significantly associated with the survival in cervical cancer patients. Our results showed that the IL-27 2905T/G genotypes were associated with decreased susceptibility and development of cervical cancer in Chinese Han population.

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MicroRNA-144 mediates metabolic shift in ovarian cancer cells by directly targeting Glut1

Abstract

Warburg effect is characterized by an increased utilization of glucose via glycolysis in cancer cells, even when enough oxygen is present to properly respire. Recent studies demonstrate that deregulation of microRNAs contributes to the Warburg effect. In the present study, we show that miR-144 is downregulated while glucose transporter 1 (Glut1) is upregulated in ovarian cancers. In vitro studies further showed that miR-144 inhibits Glut1 expression through targeting its 3′-untranslated region. As a result, cells overexpressing miR-144 exhibited a metabolic shift, including enhanced glucose uptake and lactate production. The altered glucose metabolism induced by miR-144 also leads to a rapid growth of ovarian cancer cells. Taken together, our results indicate that miR-144 may serve as a molecular switch to regulate glycolysis in ovarian cancer by targeting the expression of Glut1.

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Impact of IGF-1 , IGF-1R , and IGFBP-3 promoter methylation on the risk and prognosis of esophageal carcinoma

Abstract

The aim of this study is to investigate IGF-1, IGF-1R, and IGFBP-3 methylations in esophageal carcinoma (EC) patients and their relationship with the development and prognosis of EC. This study population consisted of 264 patients (case group) whom EC radical resection was performed and 283 healthy individuals (control group). Methylation-specific PCR (MSP) detected the methylation status of IGF-1, IGF-1R, and IGFBP-3 in the peripheral blood in both groups. The expressions of IGF-1, IGF-1R, and IGFBP-3 in EC and adjacent normal tissues were detected by immunohistochemistry (IHC). The methylation rates of IGF-1, IGF-1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 in the case group were higher than those in the control group (all P < 0.05). Additionally, there were statistical significances for the methylation rates of IGF-1, IGF-1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 IGF-1 among patients of different clinicopathological features (all P < 0.05). The positive expression rates of IGF-1 and IGF-1R in EC were significantly higher than those in adjacent normal tissues (both P < 0.001), and the rate of IGFBP-3 in EC was significantly lower than that in adjacent normal tissues (P < 0.05). Correlation analysis showed that IGF-1 and IGF1R gene promoter methylation was positively correlated with the positive expressions of IGF-1 (r = 0.139, P = 0.024) and IGF-1R (r = 0.135, P = 0.028), while the IGFBP3 methylation was negatively correlated with the positive expression of IGFBP3 (r = −0.133, P = 0.031). The positive expressions of IGF-1, IGF-1R, and IGFBP-3 were related to different clinicopathological features (all P < 0.05). Cox multivariate analysis results showed that methylation status of IGF-1, IGF-1R, and IGF-1 + IGF1R + IGFBP3 ; expressions of IGF-1 and IGF-1R protein; infiltration depth; and lymph node metastasis (LNM) were independent factors of EC prognosis. Our study demonstrated that methylation of IGF-1, IGF1R, IGFBP3, and IGF-1 + IGF1R + IGFBP3 was closely linked with the occurrence of EC and patients' clinicopathological features. Besides, the methylation status of the target genes and the expressions of IGF-1 and IGF-1R protein were independent factors of EC prognosis, which could provide a direction for the prognosis and treatment of EC.

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Erratum to: c-Myc-regulated long non-coding RNA H19 indicates a poor prognosis and affects cell proliferation in non-small-cell lung cancer

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Pseudogene-expressed RNAs: a new frontier in cancers

Abstract

Over the past decade, the importance of non-protein-coding functional elements in the human genome has emerged from the water and been identified as a key revelation in post-genomic biology. Since the completion of the ENCODE (Encyclopedia of DNA Elements) and FANTOM (Functional Annotation of Mammals) project, tens of thousands of pseudogenes as well as numerous long non-coding RNA (lncRNA) genes were identified. However, while pseudogenes were initially regarded as non-functional relics littering the human genome during evolution, recent studies have revealed that they play critical roles at multiple levels in diverse physiological and pathological processes, especially in cancer through parental-gene-dependent or parental-gene-independent regulation. Herein, we review the current knowledge of pseudogenes and synthesize the nascent evidence for functional properties and regulatory modalities exerted by pseudogene-transcribed RNAs in human cancers and prospect the potential as molecular signatures in cancer reclassification and tailored therapy.

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SphK1 promotes tumor cell migration and invasion in colorectal cancer

Abstract

Colorectal cancer (CRC) is one of the most common cancers worldwide. Sphingosine kinase 1 (SphK1), which phosphorylates sphingosine to sphingosine-1-phosphate (S1P), is overexpressed in various types of cancers and may act as an oncogene in tumorigenesis. However, little is known about the role of SphK1 in CRC patients. We studied the expression of SphK1 in 85 cases of CRC tissues by immunohistochemistry, qRT-PCR, and western blot. We also evaluated the effect of SphK1 on cell proliferation and invasion by MTT and transwell invasion assay. SphK1 is overexpressed in CRC tissues and cell lines, and upregulation of SphK1 correlated significantly with the following parameters: lymph node metastasis, liver metastasis, and advanced TNM stage. SphK1 knockdown results in inhibition of cancer cell proliferation. Inhibition of CRC cell migration and invasion is also evident through reversal of EMT by increases in E-cadherin expression and decreases in vimentin expression. In conclusion, SphK1 is associated with the proliferation and invasiveness of CRC cells and the SphK1 gene may contribute to a novel therapeutic approach against CRC.

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Circulating long noncoding RNA GAS5 as a potential biomarker in breast cancer for assessing the surgical effects

Abstract

Long noncoding RNAs (lncRNAs) play a vital role in tumorigenesis. Until now, the value of circulating lncRNAs in the diagnosis of breast cancer (BC) has remained unknown. Here, we have explored the clinical significance of lncRNAs GAS5 and H19 in BC patients. Total RNA in the plasma was extracted from 90 preoperative BC patients, 39 postoperative BC patients, and 76 healthy controls. The expression levels were measured by quantitative real-time PCR. The potential associations between GAS5, H19 levels, and patients' clinical characteristics were analyzed. No significant differences were found between the BC patients and the healthy controls in the expression levels of GAS5 (P = 0.441) and H19 (P = 0.554), normalized by GAPDH. Plasma GAS5 exhibited correlations with the Ki67 proliferation index in 90 preoperative BC patients (P = 0.012). Compared with paired preoperative plasma, the postoperative levels of GAS5 and H19 significantly decreased in 71.8 % of BC patients (28/39) and 82.1 % of BC patients (32/39), respectively. Analysis in the 39 paired preoperative and postoperative plasma samples showed that lower GAS5 levels appeared in the patients with a high Ki67 proliferation index before surgery (P = 0.012) and the patients with a positive lymph node metastasis state after surgery (P = 0.029). Plasma lncRNA GAS5 may have the potential to assess the surgical effects and prognosis for BC patients.

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miR-615-5p prevents proliferation and migration through negatively regulating serine hydromethyltransferase 2 (SHMT2) in hepatocellular carcinoma

Abstract

It has been reported that miR-615-5p was upregulated in hepatocellular carcinoma (HCC) preventing both growth and migration. However, the underlying mechanism by which miR-615-5p played a role in HCC remains unknown. Here, in our present study, to investigate the mechanism of miR-615-5p, bioinformatic prediction and luciferase reporter assay were employed to ascertain the downstream target of miR-615-5p finding that the serine hydromethyltransferase 2 (SHMT2) was the direct downstream target. Knockdown or overexpression of miR-615-5p can lead to increasing or decreasing expression of SHMT2 in HCC cells. Besides, knockdown or overexpression of SHMT2 can suppress or promote both proliferation and migration of HCC cells, indicating that miR-615-5p can directly and negatively regulate the SHMT2 in HCC cells. In addition, to understand the clinicopathological significance of SHMT2 expression in HCC, immunohistochemistry was performed. It was found that SHMT2 expression was significantly associated with poor prognosis and TNM stage. Together, our results for the first time showed that miR-615-5p prevents proliferation and migration through negatively regulating SHMT2 in HCC.

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G12V and G12A KRAS mutations are associated with poor outcome in patients with metastatic colorectal cancer treated with bevacizumab

Abstract

The v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are found in 35–45 % of colorectal cancer (CRC) cases. Although the association between the RAS signaling and angiogenesis is well known, the negative predictive value of KRAS mutation has not been established in patients treated with bevacizumab. The aim of this study was to evaluate the association between specific KRAS mutation types and outcome of patients with metastatic CRC treated with bevacizumab. The study included 404 patients with metastatic CRC (mCRC) treated with bevacizumab. Clinical data obtained from the clinical registry CORECT were retrospectively analyzed. The shortest survival was observed in patients with tumors harboring G12V or G12A KRAS mutation (G12V/A). The median progression-free survival (PFS) and overall survival (OS) for patients with tumors harboring G12V/A KRAS mutation was 6.6 and 16.8 compared to 11.6 and 26.3 months for patients with tumors harboring other KRAS mutation type (p < 0.001 and p < 0.001), while the survival of patients harboring other KRAS mutation types was comparable to those with tumors harboring wild-type KRAS gene. In the Cox multivariable analysis, KRAS G12V/A mutation type remains a significant factor predicting both PFS (HR = 2.18, p < 0.001) and OS (HR = 2.58, p < 0.001). In conclusion, the results of the present study indicate that there is a significant difference in biological behavior between tumors harboring G12V/A and other KRAS mutations. Moreover, comparison of the survival of patients with tumors harboring G12V/A KRAS mutations with those harboring wild-type KRAS gene revealed that G12V/A KRAS mutations are prognostic biomarker for inferior PFS and OS in patients with mCRC treated with bevacizumab in univariate as well as multivariable analyses.

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Decreased expression of MEG3 contributes to retinoblastoma progression and affects retinoblastoma cell growth by regulating the activity of Wnt/β-catenin pathway

Abstract

The aberrant expression of MEG3 has been found in some types of cancers; however, little is known concerning the function of MEG3 in retinoblastoma. To elucidate the roles of MEG3 in retinoblastoma, MEG3 expression was quantified in 63 retinoblastoma samples and corresponding nontumor tissues in this work. Moreover, retinoblastoma cell lines were transfected with pcDNA3.1-MEG3 or si-MEG3, after which proliferation, apoptosis, and expression of β-catenin were assayed. TOP-Flash reporter assay was also used to investigate the activity of the Wnt/β-catenin pathway. The results showed that MEG3 was downregulated in retinoblastoma tissues, and the level of MEG3 was negatively associated with IIRC stages and nodal or distant metastasis. More importantly, Kaplan-Meier survival analysis demonstrated that patients with low MEG3 expression had poorer survival and multivariate Cox regression analysis revealed that MEG3 was an independent prognostic factor in retinoblastoma patients. We also observed that MEG3 expression can be modulated by DNA methylation by using 5-aza-CdR treatment. In addition, overexpression of MEG3 suppressed proliferation, promoted apoptosis, and influences the activity of the Wnt/β-catenin pathway in retinoblastoma cell lines. Furthermore, we found that Wnt/β-catenin pathway activator rescued the anticancer effect of MEG3 in retinoblastoma. In conclusion, our study for the first time demonstrated that MEG3 was a tumor suppressor by negatively regulating the activity of the Wnt/β-catenin pathway in the progression of retinoblastoma and might serve as a prognostic biomarker and molecular therapeutic target.

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miR-27a regulates the sensitivity of breast cancer cells to cisplatin treatment via BAK-SMAC/DIABLO-XIAP axis

Abstract

MicroRNA-27a (miR-27a) has been reported to be an onco-microRNA in multiple cancers promoting tumor growth and metastasis, but the role of miR-27a in regulating the cancer sensitivity to chemotherapy remains unknown. In this study, upregulation of miR-27a was validated by real-time PCR analysis in breast cancer (BC) cell lines and samples of BC patients. A negative correlation between miR-27a and bak was also observed in normal breast epithelial cell line MCF-10A and BC cell lines, suggesting that the bak is the potential target of miR-27a. miR-27a could modulate the growth and metastasis of BC cells. More importantly, we found that knockdown of miR-27a by the specific inhibitors significantly increased the sensitivity of T-47D cells to cisplatin (CDDP) treatment. After further investigation, we indicated that the knockdown of miR-27a promoted the apoptosis via mitochondrial pathway in T-47D cells treated with CDDP, depending on the BAK-second mitochondria-derived activator of caspase/direct IAP binding protein with low pI (SMAC/DIABLO)-X-linked inhibitor of apoptosis (XIAP) axis. Interestingly, we found that the sensitivity of T-47D cells to some other chemotherapeutic agents (5-fluorouracil, doxorubicin, and tumor necrosis factor-related apoptosis-inducing ligand) was also regulated by miR-27a. These findings improve our understanding of the role of miR-27a in breast cancer and might provide a novel strategy for cancer therapy.

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Lysophosphatidic acid activates the RhoA and NF-κB through Akt/IκBα signaling and promotes prostate cancer invasion and progression by enhancing functional invadopodia formation

Abstract

We have demonstrated previously that increased RhoA and nuclear factor (NF)-κB activities are associated with increased PC-3 prostate cancer cell invasion and that lysophosphatidic acid (LPA) significantly increases cancer invasion through RhoA and NF-κB activation. In this study, we identified the intermediate signaling molecules and specialized cell structures which are activated by LPA, resulting in enhanced cellular invasion. LPA-induced Akt and IκBα signaling pathways were necessary for RhoA and NF-κB activation, and these LPA effects were abolished by RhoA inhibition. Mice injected with PC-3 cells expressing dominant-negative RhoA N19 developed significantly less tumor growth compared with those injected with control (pcDNA 3.1). In addition, LPA treatment increased functional invadopodia formation. Activation of RhoA and NF-κB through the Akt and IκBα signaling pathway was required for LPA-stimulated gelatin degradation activity. LPA administration increased tumor growth and osteolytic lesions in a mouse xenograft model. These results indicate that LPA promotes PC-3 cell invasion by increasing functional invadopodia formation via upregulating RhoA and NF-κB signaling which contributes to prostate cancer progression. Therefore, the LPA and RhoA-NF-κB signaling axis may represent key molecular targets to inhibit prostate cancer invasion and progression.

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Increasing radiation dose improves immunotherapy outcome and prolongation of tumor dormancy in a subgroup of mice treated for advanced intracerebral melanoma

Abstract

Previously, we developed a clinically relevant therapy model for advanced intracerebral B16 melanomas in syngeneic mice combining radiation and immunotherapies. Here, 7 days after B16-F10-luc2 melanoma cells were implanted intracerebrally (D7), syngeneic mice with bioluminescent tumors that had formed (1E10⁵ to 7E10⁶ photons per minute (>1E10⁶, large; <1E10⁶, small) were segregated into large-/small-balanced subgroups. Then, mice received either radiation therapy alone (RT) or radiation therapy plus immunotherapy (RT plus IT) (single injection of mAbPC61 to deplete regulatory T cells followed by multiple injections of irradiated granulocyte macrophage colony stimulating factor transfected B16-F10 cells) (RT plus IT). Radiation dose was varied (15, 18.75 or 22.5 Gy, given on D8), while immunotherapy was provided similarly to all mice. The data support the hypothesis that increasing radiation dose improves the outcome of immunotherapy in a subgroup of mice. The tumors that were greatly delayed in beginning their progressive growth were bioluminescent in vivo—some for many months, indicating prolonged tumor "dormancy," in some cases presaging long-term cures. Mice bearing such tumors had far more likely received radiation plus immunotherapy, rather than RT alone. Radiotherapy is a very important adjunct to immunotherapy; the greater the tumor debulking by RT, the greater should be the benefit to tumor immunotherapy.

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Increasing radiation dose improves immunotherapy outcome and prolongation of tumor dormancy in a subgroup of mice treated for advanced intracerebral melanoma

Abstract

Previously, we developed a clinically relevant therapy model for advanced intracerebral B16 melanomas in syngeneic mice combining radiation and immunotherapies. Here, 7 days after B16-F10-luc2 melanoma cells were implanted intracerebrally (D7), syngeneic mice with bioluminescent tumors that had formed (1E10⁵ to 7E10⁶ photons per minute (>1E10⁶, large; <1E10⁶, small) were segregated into large-/small-balanced subgroups. Then, mice received either radiation therapy alone (RT) or radiation therapy plus immunotherapy (RT plus IT) (single injection of mAbPC61 to deplete regulatory T cells followed by multiple injections of irradiated granulocyte macrophage colony stimulating factor transfected B16-F10 cells) (RT plus IT). Radiation dose was varied (15, 18.75 or 22.5 Gy, given on D8), while immunotherapy was provided similarly to all mice. The data support the hypothesis that increasing radiation dose improves the outcome of immunotherapy in a subgroup of mice. The tumors that were greatly delayed in beginning their progressive growth were bioluminescent in vivo—some for many months, indicating prolonged tumor "dormancy," in some cases presaging long-term cures. Mice bearing such tumors had far more likely received radiation plus immunotherapy, rather than RT alone. Radiotherapy is a very important adjunct to immunotherapy; the greater the tumor debulking by RT, the greater should be the benefit to tumor immunotherapy.

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Targeting the microenvironment of pancreatic cancer: overcoming treatment barriers and improving local immune responses

Abstract

Historically, patients diagnosed with metastatic pancreatic cancer have faced a grim prognosis. The survival benefit seen with systemic chemotherapies and even combinations thereof have been disappointing. However, growing data suggest that the microenvironment of pancreatic cancer may be contributing to this poor prognosis. This microenvironment has a dense fibrotic stroma, and is hypoxic and highly immunosuppressive, all of which pose barriers to treatment. Newer strategies looking to disrupt the fibrotic stroma, target hypoxic areas, and improve local immune responses in the tumor microenvironment are currently undergoing clinical evaluation and seem to offer great promise. In addition to these therapies, preclinical work evaluating novel cytotoxic agents including nanoparticles has also been encouraging. While much research still needs to be done, these strategies offer new hope for patients with pancreatic cancer.

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Vaginal-cuff control and toxicity results of a daily HDR brachytherapy schedule in endometrial cancer patients

Abstract

Purpose

To analyze the vaginal-cuff local control (VCC) and toxicity in postoperative endometrial carcinoma patients (EC) underwent high-dose-rate brachytherapy (HDR-BT) administered daily.

Materials and methods

154 consecutive patients received postoperative HDR-BT for EC from January 2007 to September 2011. FIGO-staging I–IIIC2 patients were divided into two groups according to risk classification: Group 1 (94/154) included high-risk or advanced disease patients and Group 2 (60/154) included intermediate-risk EC patients. Group 1 underwent external beam irradiation (EBI) plus HDR-BT (2 fractions of 5 Gy) and Group 2 underwent HDR-BT alone (4 fractions of 5 Gy). Toxicity evaluation was done with RTOG scores for bladder and rectum, and the objective criteria of LENT–SOMA for vagina.

Results

With a median follow-up of 46.7 months (36.6–61 months) only two patients developed vaginal-cuff recurrence in Group 1 (2.1 %) and none in group 2 (0 %). Early toxicity in Group 1 appeared 5.3 % in rectum, 7.5 % in bladder (G1–G2) and 2.1 % in vagina (G1); late toxicity was present in 7.3 % in rectum (all G1–G2 but 1 G3) and in 27.7 % in vagina (all G1–G2 but one G4). In Group 2, 6.7 % developed acute G1–G2 bladder and 6.6 % acute vaginal (G1–G2) toxicity. No late rectal or bladder toxicity was observed; 21.7 % of G1–G2 presented late problems in vagina.

Conclusions

The present HDR-BT schedule of 2 fractions of 5 Gy after EBI and 4 fractions of 5 Gy administered daily showed excellent results in terms of VCC and toxicity.

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Increasing radiation dose improves immunotherapy outcome and prolongation of tumor dormancy in a subgroup of mice treated for advanced intracerebral melanoma

Abstract

Previously, we developed a clinically relevant therapy model for advanced intracerebral B16 melanomas in syngeneic mice combining radiation and immunotherapies. Here, 7 days after B16-F10-luc2 melanoma cells were implanted intracerebrally (D7), syngeneic mice with bioluminescent tumors that had formed (1E10⁵ to 7E10⁶ photons per minute (>1E10⁶, large; <1E10⁶, small) were segregated into large-/small-balanced subgroups. Then, mice received either radiation therapy alone (RT) or radiation therapy plus immunotherapy (RT plus IT) (single injection of mAbPC61 to deplete regulatory T cells followed by multiple injections of irradiated granulocyte macrophage colony stimulating factor transfected B16-F10 cells) (RT plus IT). Radiation dose was varied (15, 18.75 or 22.5 Gy, given on D8), while immunotherapy was provided similarly to all mice. The data support the hypothesis that increasing radiation dose improves the outcome of immunotherapy in a subgroup of mice. The tumors that were greatly delayed in beginning their progressive growth were bioluminescent in vivo—some for many months, indicating prolonged tumor "dormancy," in some cases presaging long-term cures. Mice bearing such tumors had far more likely received radiation plus immunotherapy, rather than RT alone. Radiotherapy is a very important adjunct to immunotherapy; the greater the tumor debulking by RT, the greater should be the benefit to tumor immunotherapy.

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Unusual Thyroid Carcinoma Metastases: a Case Series and Literature Review

Abstract

The most common sites of metastatic differentiated thyroid cancer are the neck lymph nodes, while distant metastases typically involve the lungs, the bones, and less frequently the brain. Uncommon metastatic sites include the liver, adrenal gland, kidney, pancreas, and skin. The epidemiological aspects of thyroid metastases in rare sites are largely unknown and their identification could have a significant impact on patients management. A mini-series of unusual metastatic sites of thyroid carcinoma is proposed as a contribution to current knowledge on anatomopathological characteristics and clinical outcome. Of the six cases that were assessed, the metastases were the following: skin metastases (2), skin and pancreas metastases (1), renal metastasis (1), adrenal metastasis (1), and liver metastasis (1). In our experience, metastases in rare sites do not always represent a negative prognostic factor for disease outcome. In fact they can occur as single distant lesion and if surgically resectable, their treatment can also lead to local disease remission.

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STK11 Mutation Identified in Thyroid Carcinoma

Abstract

Peutz-Jeghers syndrome (PJS) is an autosomal-dominant disorder, in which germline mutation of serine threonine-protein kinase 11 (STK11) is identified in up to 90 % of the patients who meet clinical criteria for PJS. Hematoxylin and eosin (H&E) slides of the tumor were reviewed to confirm areas with at least 25 % of tumor cellularity. Then, the designated area was extracted for genomic DNA. Targeted next-generation sequencing analysis was performed using a 47-gene panel. Case 1 is a 71-year-old man with high grade follicular thyroid carcinoma with clear cell and oncocytic features. The carcinoma showed a missense mutation in TP53 (p.R342G, c.1024C > G) and a 16-nucleotide intronic deletion started next to the 3′ of exon 6 (involving the canonical +1 and +2 bases of the splice donor site) in STK11 (p.?, c.862 + 1_862 + 16delGTGGGAGCCTCATCCC). Case 2 is a 76-year-old woman with tall cell variant papillary thyroid carcinoma. The carcinoma demonstrated a missense mutation in BRAF (p.V600E, c.1799T > A) and a missense mutation in STK11 (p.F354L, c.1062C > G). In summary, we present two elderly patients with thyroid carcinoma harboring STK11 mutation without clinical manifestation of PJS. The findings suggest that STK11 may play a role in thyroid carcinoma development.

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Outcomes of a Clinical Pathway for Borderline Resectable Pancreatic Cancer

Abstract

Background

Without prospective data establishing a consensus multimodality approach to borderline resectable pancreatic adenocarcinoma, institutional treatment regimens vary. This study investigated the outcomes of the clinical pathway at the author's institution, which consists of neoadjuvant gemcitabine, docetaxel, capecitabine, and stereotactic radiotherapy followed by surgery.

Methods

The study reviewed all cases that met the National Comprehensive Cancer Network (NCCN) diagnostic criteria for borderline resectable pancreatic adenocarcinoma from 1 January 2006, to 31 December 2013. Pancreatectomy rates, margin status, pathologic response, disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) were retrospectively examined. Standard statistical methods and Kaplan–Meier survival analysis were used for statistical comparisons.

Results

Of 121 patients who met criteria, 101 entered the clinical pathway, and 94 (93.1 %) completed neoadjuvant chemotherapy and radiation therapy. Of the 101 patients, 55 (54.5 %) underwent pancreatectomy, with 53 patients (96.4 %) having microscopically negative margins (R0) and 2 patients (3.6 %) having microscopically positive margins (R1). Vascular resection was required for 22 patients (40 %), with rates of 95.5 % for R0 (n = 21) and 4.5 % for R1 (n = 1). A pathologic response to treatment was demonstrated by 45 patients (81.8 %) and a complete response by 10 patients (14.5 %). Pancreatectomy resulted in a median DFS of 23 months (95 % conflidence interval [CI] 14.5–31.5), a median DSS of 43 months (95 % CI, 25.7–60.3), and a median OS of 33 months (95 % CI, 25.0–41.0) versus a median DSS and OS of 14 months (95 % CI, 10.9–17.1) for patients without pancreatectomy (DSS: P = 3.5 × 10⁻¹³; OS: P = 4.7 × 10⁻¹⁰).

Conclusions

The study demonstrated high rates for neoajduvant therapy completion (93.1 %) and pancreatectomy (54.5 %). After pancreatectomy, DSS was significantly improved (43 months), with a pathologic response demonstrated by 81.8 % and a complete response by 14.5 % of the patients. The results support further study of this borderline resectable pancreatic adenocarcinoma clinical pathway.

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Cervical Cancer Prevention in Malaysia: Knowledge and Attitude of Undergraduate Pharmacy Students Towards Human Papillomavirus Infection, Screening and Vaccination in Malaysia

Abstract

This study was conducted to evaluate knowledge of undergraduate pharmacy students about human papillomavirus infection and their attitude towards its prevention. A cross-sectional survey was conducted in 270 undergraduate pharmacy students using a validated questionnaire to assess knowledge about human papillomavirus infection and cervical cancer and their attitudes towards human papillomavirus vaccines. Eighty-one percent of the respondents knew that human papillomavirus is a cause of cervical cancer, and 87.8 % knew that this infection is preventable. The gender of the respondents showed the strongest correlations with human papillomavirus knowledge. There were no significant correlations between the ethnic group of the respondents and their human papillomavirus-related knowledge. Higher perceptions of risk were associated with relationship status, and respondents who were in a relationship showed greater interest in vaccinating themselves; relationship status emerged as a unique predictor. The results indicated a moderately high level of knowledge and positive attitude towards human papillomavirus vaccination with few disagreements. The results of this study will help to develop and plan appropriate education campaigns for pharmacy students that aim to reduce human papillomavirus infection and, consequently, the incidence of and mortality caused by cervical cancer in Malaysia.

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Databases as Vehicles for Comparative Effectiveness Research

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Screening Performance for Frailty Among Older Patients With Cancer: A Cross-Sectional Observational Study of Two Approaches

Objectives: To investigate the screening performance for frailty of the Vulnerable Elders Survey-13 (VES-13) and the 2-step approach consisting of the VES-13 plus the anhedonia (loss of interest or pleasure) item from Patient Health Questionnaire-9 (PHQ-9) among older patients with newly diagnosed cancer. Methods: This study involved 106 consecutive inpatients aged 65 years or older, newly diagnosed with malignant lymphoma or multiple myeloma, just before chemotherapy initiation. The participants were administered the VES-13, and also underwent a comprehensive geriatric assessment (CGA), including for depression and 6 other geriatric conditions, using validated measures, just before initiation of chemotherapy. We defined frailty as the presence of 2 or more geriatric conditions as determined by the CGA. Receiver operating characteristic analysis was performed. The 2-step screening approach was examined by post hoc analysis. Results: The average age of the subjects was 74 years. Among the 106 subjects, 50% met the criteria for frailty. Using a cutoff score of 2 to 3 on the VES-13, a sensitivity and negative predictive value (NPV) of 72% of the screening tool was obtained for the condition of frailty. When the second step of the screening, consisting of the VES-13 plus anhedonia, was applied to the VES-13–negative patients, the sensitivity and NPV improved to 90% and 88%, respectively. Conclusions: The 2-step approach exhibited better screening performance for frailty among patients with cancer than existing methods. Large prospective studies are required in the future to confirm this ability of the 2-step approach.

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NCCN News

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Independent Prognostic Value of Serum Markers in Diffuse Large B-Cell Lymphoma in the Era of the NCCN-IPI

Background: Several serum parameters have been evaluated for adding prognostic value to clinical scoring systems in diffuse large B-cell lymphoma (DLBCL), but none of the reports used multivariate testing of more than one parameter at a time. The goal of this study was to validate widely available serum parameters for their independent prognostic impact in the era of the National Comprehensive Cancer Network–International Prognostic Index (NCCN-IPI) score to determine which were the most useful. Patients and Methods: This retrospective bicenter analysis includes 515 unselected patients with DLBCL who were treated with rituximab and anthracycline-based chemoimmunotherapy between 2004 and January 2014. Results: Anemia, high C-reactive protein, and high bilirubin levels had an independent prognostic value for survival in multivariate analyses in addition to the NCCN-IPI, whereas neutrophil-to-lymphocyte ratio, high gamma-glutamyl transferase levels, and platelets-to-lymphocyte ratio did not. Conclusions: In our cohort, we describe the most promising markers to improve the NCCN-IPI. Anemia and high C-reactive protein levels retain their power in multivariate testing even in the era of the NCCN-IPI. The negative role of high bilirubin levels may be associated as a marker of liver function. Further studies are warranted to incorporate these markers into prognostic models and define their role opposite novel molecular markers.

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Paying Less for High-Value Care--Are You Kidding Me?

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PSA Screening for Prostate Cancer: Why Saying No is a High-Value Health Care Choice

Enthusiasm for cancer screening and treatment of screen-detected cancer has led to widespread prostate-specific antigen (PSA) screening, a marked increase in prostate cancer incidence, and high use of surgical, radiation, and androgen deprivation treatment for screen-detected disease. This has occurred in advance of a full understanding of the clinical and financial tradeoffs. Although questions remain whether lifetime benefits outweigh harms and costs, data indicate that this balance is not favorable through at least 15 years. This article outlines a conceptual framework for determining the value of screening strategies according to screening and treatment intensity. We describe 4 main cancer screening goals and examine whether PSA screening and treatment achieve these goals and thus provide high-value care. Available evidence demonstrates that PSA screening provides at best a small reduction in prostate cancer mortality, and no reduction in all-cause mortality. High-intensity PSA screening and treatment currently practiced in the United States result in substantial harms and large health care expenditures—it is low-value care. The health importance of prostate cancer and the financial costs to patients and society require improved detection and treatment strategies that produce greater value to patients. We propose lower-intensity, higher-value options. However, until evidence supports a higher-value alternative to current PSA screening strategies, physicians should recommend against PSA screening, policymakers should encourage reduced screening, and most men should say no to the PSA test.

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Toward Personalized Guidelines in Bladder Cancer

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Oncology Research Program

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NCCN at 20: Forward Momentum

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A Decade of Changes in Preferences for Life-Sustaining Treatments Among Terminally Ill Patients With Cancer

Background: Changes over time in preferences for life-sustaining treatments (LSTs) at end of life (EOL) in different patient cohorts are not well established, nor is the concept that LST preferences represent more than 2 groups (uniformly prefer/not prefer). Purpose: The purpose of this study was to explore heterogeneity and changes in patterns of LST preferences among 2 independent cohorts of terminally ill patients with cancer recruited a decade apart. Methods: Preferences for cardiopulmonary resuscitation, intensive care unit care, cardiac massage, intubation with mechanical ventilation, intravenous nutritional support, nasogastric tube feeding, and dialysis were surveyed among 2,187 and 2,166 patients in 2003–2004 and 2011–2012, respectively. Patterns and changes in LST preferences were examined by multigroup latent class analysis. Results: We identified 7 preference classes: uniformly preferring, uniformly rejecting, uniformly uncertain, favoring nutritional support but rejecting other treatments, favoring nutritional support but uncertain about other treatments, favoring intravenous nutritional support with mixed rejection of or uncertainty about other treatments, and preferring LSTs except intubation with mechanical ventilation. Probability of class membership decreased significantly over time for the uniformly preferring class (15.26%–8.71%); remained largely unchanged for the classes of uniformly rejecting (41.71%–40.54%) and uniformly uncertain (9.10%–10.47%), and favoring nutritional support but rejecting (20.68%–21.91%) or uncertain about (7.02%–5.47%) other treatments, and increased significantly for the other 2 classes. The LST preferences of Taiwanese terminally ill patients with cancer are not a homogeneous construct and shifted toward less-aggressive treatments over the past decade. Conclusions: Identifying LST preference patterns and tailoring interventions to the unique needs of patients in each LST preference class may lead to the provision of less-aggressive EOL care.

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Complete Response to Erlotinib and Bevacizumab in a Patient With Biphenotypic (Hepatobiliary) Primary Liver Carcinoma

Biphenotypic (hepatobiliary) primary liver carcinomas [B(H-B)PLCs] are rare tumors with features of both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). These tumors are associated with a poor overall prognosis and treatment is not well defined. Research over the past 20 years has identified aberrations in several molecular pathways, including epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in hepatocellular and biliary tract cancers. These discoveries led to the evaluation of targeted therapies, such as tyrosine kinase inhibitors, for the treatment of HCC and ICC. We report a case of a patient with metastatic B(H-B)PLC found to have a single nucleotide variant in the EGFR gene locus R521K who achieved a complete response on imaging after treatment with the combination of an EGFR inhibitor and a VEGF inhibitor. This case prompts consideration of further genomic analysis of these rare tumors and the potential use of targeted therapies in the treatment of patients with B(H-B)PLCs.

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Prostate Cancer Early Detection, Version 2.2015

Prostate cancer represents a spectrum of disease that ranges from nonaggressive, slow-growing disease that may not require treatment to aggressive, fast-growing disease that does. The NCCN Guidelines for Prostate Cancer Early Detection provide a set of sequential recommendations detailing a screening and evaluation strategy for maximizing the detection of prostate cancer that is potentially curable and that, if left undetected, represents a risk to the patient. The guidelines were developed for healthy men who have elected to participate in the early detection of prostate cancer, and they focus on minimizing unnecessary procedures and limiting the detection of indolent disease.

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Breast Cancer, Version 1.2016

These NCCN Guideline Insights highlight the important updates to the systemic therapy recommendations in the 2016 NCCN Guidelines for Breast Cancer. In the most recent version of these guidelines, the NCCN Breast Cancer Panel included a new section on the principles of preoperative systemic therapy. In addition, based on new evidence, the panel updated systemic therapy recommendations for women with hormone receptor–positive breast cancer in the adjuvant and metastatic disease settings and for patients with HER2-positive metastatic breast cancer. This report summarizes these recent updates and discusses the rationale behind them.

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The Case for Tailored Prostate Cancer Screening: An NCCN Perspective

A preponderance of clinical evidence supports a significant public health benefit for screening and early detection of prostate cancer in selected men. The challenge lies in maximizing early diagnosis of potentially aggressive but curable disease while minimizing diagnosis and treatment of indolent disease. A tailored approach to population screening in appropriately counseled men, using an evidence-based strategy with judicious prostate-specific antigen (PSA) testing, will reduce prostate-cancer mortality yet limit overdetection of clinically insignificant disease. Use of newer biomarkers that increase specificity for prostate cancer detection, including percentage of free PSA, 4Kscore, prostate health index, prostate cancer antigen 3, and multiparametric MRI may be considered under certain circumstances.

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Making the Grade: The Impact of Low-Grade Toxicities on Patient Preference for Treatment With Novel Agents

Background: Targeted therapies have shown clinical benefit in the treatment of solid tumors. The toxicity profiles and treatment duration and schedule of these agents differ considerably from those of traditional chemotherapy. Many studies of targeted therapies report sizeable numbers of grade 1 or 2 toxicities. We sought to determine whether anticipation of low-grade toxicities and treatment logistics impact patient willingness to undergo therapy. Patients and Methods: A total of 209 patients with cancer (101 lung and 108 breast) were surveyed at the Vanderbilt-Ingram Cancer Center regarding willingness to comply with treatment based on anticipated efficacy, dosing convenience, and toxicity profiles. All toxicities were Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade 1 and 2. Willingness to comply with treatment depending on toxicity, anticipated benefit, cancer type, and dosing convenience was compared. Results: A substantial number of patients (2.9%–48.8%, depending on the toxicity described) professed unwillingness to undergo treatment because of anticipated grade 1 and 2 toxicities. Gastrointestinal and constitutional toxicities had a stronger negative impact on patient willingness to undergo therapy than dermatologic toxicity. Patients with lung cancer were significantly more likely to accept dermatologic and gastrointestinal toxicities than those with breast cancer. Willingness to tolerate toxicities correlated with expected benefit in terms of life expectancy and chance of cure. Lengthy travel distance for treatment negatively impacted willingness to undergo treatment. Conclusions: Anticipation of low-grade toxicities and dosing inconvenience negatively impacts patient willingness to be treated, which may affect adherence and therapeutic outcomes from therapy. Long-term tolerability should be considered when developing and assessing the impact of novel agents.

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Management of resectable colorectal lung metastases

Abstract

Lung metastases occur in 10–20 % of patients with colorectal cancer. The biology of colorectal lung metastases is poorly understood, however lung metastases are more common in patients with rectal cancer and in patients with RAS mutations. Although the majority of patients have extrapulmonary disease, a small proportion of patients with lung metastases are suitable for lung metastasectomy and surgical resection has become a standard of care, based on data from retrospective series demonstrating a 5-year overall survival of 40–68 %. However, there remains uncertainty regarding the optimal management approach for these patients due to the lack of evidence from randomized controlled trials and current practice varies between institutions. For example, the role for neoadjuvant and adjuvant chemotherapy is not yet defined and there are no randomized trials comparing surgery with alternative treatment options such as radiofrequency ablation and stereotactic ablative radiotherapy. Further research is needed to improve the selection of patients for surgery, but favourable prognostic factors include a normal pre-operative CEA, solitary metastasis, complete resection and a long disease-free interval. There is also evidence that patients with resectable liver and lung metastases may benefit from resection of both sites of disease, and that re-resection may be of benefit in selected patients who relapse with resectable lung metastases. This article summarizes the biology of colorectal lung metastases and discusses the management of patients with lung metastases.

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5th International ACC Symposium: Old Syndromes with New Biomarkers and New Therapies with Old Medications

Abstract

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with variable but often aggressive clinical course. Hormonal overproduction can be seen in about half of all ACC cases. When present, the hormonal excess leads to a wide range of metabolic, musculoskeletal, cardiovascular, and infectious complications and adds multiple layers of complexity to the management of ACC. To improve the outcome of patients with hormonally functioning ACC, an effective approach should include parallel efforts to achieve oncologic and hormonal control. An experienced multidisciplinary team is crucial to deliver and coordinate care to manage the specific aspects of this condition. In this review, we summarized the clinical features and management of hormonally functioning ACCs to assist practicing physicians in addressing the complex medical issues that can be seen in the context of this clinical entity.

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5th International ACC Symposium: Hereditary Predisposition to Childhood ACC and the Associated Molecular Phenotype

Abstract

Adrenocortical carcinoma (ACC) affects children and adults. Roughly 50 % of very early onset ACCs occur in children with germline TP53 mutations. Several recent studies have extended our understanding in basic, clinical, and translational genetics with regard to TP53 germline predisposition in ACC patients. The recent description of the molecular landscape of pediatric ACCs provided insight into differences of tumors arising in patients with and without TP53 germline mutation. Another recent important finding is that not all TP53 mutations are equal in their tumor suppressing potential. It has now been shown that family histories as well as molecular characteristics of preserved TP53 functions vary greatly between mutations. It also has become clear that adult patients with ACC often harbor germline mutations causing hereditary syndromes, including Li-Fraumeni syndrome (LFS), Lynch syndrome, and multiple endocrine neoplasia type 1 (MEN1).

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Cancers, Vol. 7, Pages 2443-2458: Cancer-Associated Fibroblasts: Their Characteristics and Their Roles in Tumor Growth

Cancer tissues are composed of cancer cells and the surrounding stromal cells (e.g., fibroblasts, vascular endothelial cells, and immune cells), in addition to the extracellular matrix. Most studies investigating carcinogenesis and the progression, invasion, metastasis, and angiogenesis of cancer have focused on alterations in cancer cells, including genetic and epigenetic changes. Recently, interactions between cancer cells and the stroma have attracted considerable attention, and increasing evidence has accumulated on this. Several researchers have gradually clarified the origins, features, and roles of cancer-associated fibroblasts (CAFs), a major component of the cancer stroma. CAFs function in a similar manner to myofibroblasts during wound healing. We previously reported the relationship between CAFs and angiogenesis. Interleukin-6 (IL-6), a multifunctional cytokine, plays a central role in regulating inflammatory and immune responses, and important roles in the progression, including proliferation, migration, and angiogenesis, of several cancers. We showed that CAFs are an important IL-6 source and that anti-IL-6 receptor antibody suppressed angiogenesis and inhibited tumor-stroma interactions. Furthermore, CAFs contribute to drug-resistance acquisition in cancer cells. The interaction between cancer cells and the stroma could be a potential target for anti-cancer therapy.

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Hippocampal dosimetry correlates with the change in neurocognitive function after hippocampal sparing during whole brain radiotherapy: a prospective study

Whole brain radiotherapy (WBRT) has been the treatment of choice for patients with brain metastases. However, change/decline of neurocognitive functions (NCFs) resulting from impaired hippocampal neurogenesis ...

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Silencing of Human CutC Gene ( hCutC ) Induces Apoptosis in HepG2 Cells

Abstract

Copper is an essential microelement required for maintaining normal cell physiology. Copper transporter CutC is one of the six members of Cut family proteins, involved in prokaryotic copper homeostasis. Human homolog of CutC (hCutC) is an intracellular copper-binding protein with unknown physiological function. In the present study using HepG2 cells, we report the effects of hCutC knockdown on copper sensitivity and morphology of cells that ultimately leads to apoptosis. We silenced hCutC using specific small interfering RNA (siRNA), and its downregulation was confirmed by quantitative real-time PCR. Though there was no significant variation in total cellular copper as estimated by inductively coupled plasma-atomic emission spectrometry (ICP-AES), knockdown of hCutC caused an increase in sensitivity of HepG2 cells to copper loads when compared to control cells (studied by MTT-based cell viability assay). Morphological analysis by transmission electron microscopy (TEM) indicated onset of apoptosis in hCutC-silenced cells which was exacerbated upon copper treatment. Mitochondrial transmembrane potential (ΔΨm) assay and DNA fragmentation assay further ensured apoptosis occurring in cells upon hCutC silencing. The present study reveals copper induced damage in cells upon hCutC silencing and provides evidence for the role of hCutC protein in intracellular copper homeostasis.

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Prognostic value of health-related quality of life for overall survival in elderly non-small-cell lung cancer patients

Publication date: January 2016
Source:European Journal of Cancer, Volume 52
Author(s): Frédéric Fiteni, Dewi Vernerey, Franck Bonnetain, Fabien Vaylet, Hélène Sennélart, Jean Trédaniel, Denis Moro-Sibilot, Dominique Herman, Hélène Laizé, Philippe Masson, Marc Derollez, Christelle Clément-Duchêne, Bernard Milleron, Franck Morin, Gérard Zalcman, Elisabeth Quoix, Virginie Westeel
BackgroundWe investigated whether the health-related quality of life (HRQoL) score is a prognostic factor for overall survival (OS) in elderly patients with advanced non-small-cell lung cancer (NSCLC).MethodsWe included 451 NSCLC patients aged 70–89 years enrolled in the Intergroupe Francophone de Cancérologie Thoracique 0501 trial, using scores of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 at baseline to investigate the prognostic value of HRQoL for OS, in addition to conventional factors. Cox regression model was used for both univariate and multivariate analyses of OS.ResultsGlobal health status (GH) dimension score at baseline was associated with favourable OS when adjusted for clinical, functional, and histological factors (hazard ratio [HR]: 0.986; 95% confidence interval [CI]: 0.980–0.992).We distinguished three groups according to GH score: high (GH <46), intermediate (46 ≤GH ≤67), and low (GH >67) mortality risk. The median OS values were 14.5, 8.2, and 5.3 months in the low-, intermediate-, and high-risk categories, respectively (log-rank P <0.0001).In the high-risk group, doublet chemotherapy was not associated with favourable OS (HR: 0.70; 95% CI: 0.49–1.003; P=0.052), whereas in the intermediate- and low-risk groups, doublet chemotherapy was associated with favourable OS (HR: 0.72; 95% CI: 0.54–0.96; P=0.023 and HR: 0.50; 95% CI: 0.30–0.84; P=0.0089, respectively).ConclusionThis study supports the additional prognostic value of HRQoL data at diagnosis to identify vulnerable subpopulations in elderly NSCLC patients. HRQoL could thus be valuable in selecting patients who will benefit from doublet chemotherapy.



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Observer variability in RECIST-based tumour burden measurements: a meta-analysis

Publication date: January 2016
Source:European Journal of Cancer, Volume 53
Author(s): Soon Ho Yoon, Kyung Won Kim, Jin Mo Goo, Dong-Wan Kim, Seokyung Hahn
BackgroundResponse Evaluation Criteria in Solid Tumours (RECIST)-based tumour burden measurements involve observer variability, the extent of which ought to be determined.MethodsA literature search identified studies on observer variability during manual measurements of tumour burdens via computed tomography according to the RECIST guideline. The 95% limit of agreement (LOA) values of relative measurement difference (RMD) were pooled using a random-effects model.ResultsTwelve studies were included. Pooled 95% LOAs of RMD in measuring unidimensional longest diameters of single lesions ranged from −22.1% (95% confidence interval [CI], −30.3% to −14.0%) to 25.4% (95% CI, 17.2% to 33.5%) between observers and −17.8% (95% CI, −23.6% to −11.9%) to 16.1% (95% CI, 10.1% to 21.8%) for a single observer. Pooled 95% LOAs of RMD in measuring the sum of multiple lesions ranged from −19.2% (95% CI, −23.7% to −14.9%) to 19.5% (95% CI, 15.2% to 23.9%) between observers, and −9.8% (95% CI, −19.0% to −0.3%) to 13.1% (95% CI, 3.6% to 22.6%) for a single observer. Pooled 95% LOA of RMD in calculating the interval change of tumour burden with a single lesion ranged from −31.3% (95% CI, −46.0% to −16.5%) to 30.3% (95% CI, 15.3% to 44.8%) between observers. Studies on calculating the interval change of tumour burden for a single observer or with multiple lesions were lacking.ConclusionInterobserver RMD in measuring single tumour burden and calculating its interval change may exceed the 20% cut-off for progression. Variability decreased when tumour burden was measured by a single observer or assessed by the sum of multiple lesions.



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Survival impact of postoperative body mass index in gastric cancer patients undergoing gastrectomy

Publication date: January 2016
Source:European Journal of Cancer, Volume 52
Author(s): Han Hee Lee, Jae Myung Park, Kyo Young Song, Myung-Gyu Choi, Cho Hyun Park
BackgroundThe relationship between preoperative body mass index (BMI) and the survival of postoperative gastric cancer patients is not clear. Furthermore, the survival impact with postoperative BMI is not known, even though weight loss is inevitable after gastrectomy.MethodsPatients who underwent gastrectomy for gastric cancer between 2000 and 2008 were included in the study (n = 1909). Patients were divided into three groups based on their BMIs: low (<18.5 kg/m²), normal (18.5–24.9 kg/m²), and high BMI (≥25.0 kg/m²). Patient survival was compared according to BMI at two time points: baseline and 1 year after surgery.ResultsRegarding BMI 1 year after surgery, overall survival, disease-specific survival, and recurrence-free survival were longer in the high BMI group than the low and normal BMI groups. In a Cox proportional hazards model, adjusting for the patient's age, sex, type of surgery, tumour stage, histology, curative resection, and BMI at baseline, a high BMI 1 year after surgery was associated with lower overall mortality compared to normal BMI (hazard ratio 0.51; 95% confidence interval, 0.26–0.98). However, BMI at baseline was not an independent prognostic factor.ConclusionBMI 1 year after surgery significantly predicted the long-term survival of patients with gastric cancer compared with the preoperative BMI.



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Two cases of immune thrombocytopenia associated with pembrolizumab

Publication date: Available online 10 December 2015
Source:European Journal of Cancer
Author(s): Audrey Le Roy, Emmanuelle Kempf, Felix Ackermann, Emilie Routier, Caroline Robert, Anthony Turpin, Aurélien Marabelle, Christine Mateus, Jean-Marie Michot, Olivier Lambotte




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Perspectives of Low-Income African-American Women Non-adherent to Mammography Screening: the Importance of Information, Behavioral Skills, and Motivation

Abstract

Although information-motivation-behavioral skills (IMB) adherence model has been successfully used in many illness domains and with other populations, it has not been used in understanding mammogram screening among low-income African-American women. Thus, a qualitative examination is needed to theoretically and collectively understand the barriers to screening, given the disparities in breast cancer mortality rates among this population. Semi-structured telephone interviews were conducted with 28 low-income uninsured and underinsured African-American women, 40 to 70 years, who had not had a mammogram within the past 12 months. Women were recruited from 21 hair and nail salons and Laundromats within the five North St. Louis city zip codes with the highest breast cancer mortality rates. Transcripts were analyzed and rooted in grounded theory. This study found that the individual relevancy of information, behavioral skills—both procedural and systematic—and motivation seemed to affect screening adherence; (the results suggest the importance of reordering traditional IMB components into the following sequential order: information, behavioral skills, and motivation (IBM)). Future analyses should include a larger, more representative sample of unscreened women, in which quantitative statistical analyses could be conducted to assist in strengthening assertions about information, behavioral skills, and motivational aspects and their relationship to screening.

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Oral Cancer Knowledge and Diagnostic Ability Among Dental Students

Abstract

The purpose of this study is to examine factors that influence the diagnostic ability of dental students with regards to oral cancer and oral potentially malignant disorders. Dental students at different levels of study were directly interviewed to examine their oral cancer knowledge and diagnostic ability using a validated and pre-tested survey instrument containing validated clinical images of oral cancer and oral potentially malignant disorders. An oral cancer knowledge scale (0 to 31) was generated from correct responses on oral cancer general knowledge, and a diagnostic ability scale (0 to 100) was generated from correct selections of suspicious oral lesions. Knowledge scores ranged from 0 to 27 (mean 10.1 ± 6.0); mean knowledge scores increased with year of study; 5th year students had the highest mean knowledge score (19.1 ± 4.0), while 1st year students had the lowest (5.6 ± 3.5). Diagnostic ability scores increased with year of study and ranged from 0 to 88.5 % (mean 41.8 % ± 15.6). The ability to recognize suspicious oral lesions was significantly correlated with knowledge about oral cancer and oral potentially malignant disorders (r = 0.28; P < 0.001). There is a need to improve oral cancer education curricula; increasing students' contact with patients who have oral lesions including oral cancer will help to improve their future diagnostic ability and early detection practices.

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